Medical devices incorporating carbon nanotube material and methods of fabricating same

ABSTRACT

The present invention relates generally to medical devices; in particular and without limitation, to unique electrodes and/or electrical lead assemblies for stimulating cardiac tissue, muscle tissue, neurological tissue, brain tissue and/or organ tissue; to electrophysiology mapping and ablation catheters for monitoring and selectively altering physiologic conduction pathways; and, wherein said electrodes, lead assemblies and catheters optionally include fluid irrigation conduit(s) for providing therapeutic and/or performance enhancing materials to adjacent biological tissue, and wherein each said device is coupled to or incorporates nanostructure or materials therein. The present invention also provides methods for fabricating, deploying, and operating such medical devices.

CROSS REFERENCE TO RELATED APPLICATIONS

This non-provisional patent application hereby claims the benefit ofprovisional U.S. patent application Ser. No. 60/431,330 filed 6 Dec.2002 and entitled, “Medical Devices Incorporating Carbon NanotubeMaterial and Methods of Fabricating Same,” the entire contents of whichare hereby incorporated by reference as if fully set forth herein.

This non-provisional patent application also incorporates the contentsof co-pending non-provisional U.S. patent application Ser. No.10/262,046 filed 2 Oct. 2002 and entitled, “Active Fluid DeliveryCatheter.”

FIELD OF THE INVENTION

The present invention relates generally to medical device and; inparticular, to electrodes and/or electrical lead assemblies.

BACKGROUND OF THE INVENTION

Medical electrical leads typically incorporate at least one electrodeand the lead assembly is compact and resilient, yields a low thresholdfor stimulation, senses the low amplitude electrical signals naturallygenerated by a body. In addition, such leads should be biocompatiblewith the adjacent body tissue and body fluids, which it contacts.Various attempts have been made to improve these characteristics,especially with respect to medical electrodes electrically coupled tothe lead body of a cardiac pacing lead. Generally these attempts areaimed at increasing the interfacial, or active, surface area of anelectrode by the use of surface treatments or coatings that areconsidered highly biocompatible.

As is known in the art, electrochemical reactions occur at theelectrode-tissue interface when an electrical stimulation pulse isdelivered through a medical electrical lead assembly. This phenomenon isreferred to as “polarization,” which is known to interfere withefficient delivery of the stimulation pulses. High interfacial impedancedue to the effects of polarization reduces the effective charge transferof the stimulation pulse to the targeted tissue. Therefore lowpolarization electrodes have been developed to reduce this effect andimprove the transfer of charge from the electrode to the tissue.

One method for reducing polarization effects is to increase electrodesurface area. However, a design trade-off exists in increasing theelectrode size since medical leads and the electrodes they carry arepreferably of small dimensions such that they may be easily implanted.For example, presently available cardiac pacing leads typically havecross-sectional diameters of greater than about three or four French anda typical diameter of an electrophysiology catheter is about six French.For reference, a single French unit of measurement equals one third of amillimeter. In any event, to overcome this trade-off, methods forincreasing the active surface area of a geometrically down-sizedelectrode have been proposed. For example, treatments or coatings thatyield a porous, irregular or grooved surface increase the active surfacearea of the electrode and thereby diminish the effects of polarization.Various coatings have been proposed and put into commercial use forproducing low polarization electrodes such as platinum black, pyrolyticcarbon, iridium oxide, vitreous carbon, titanium nitride and others.

A further benefit of increasing electrode interfacial or active surfacearea can be improved electrode sensing performance. Cardiac signals,including action potentials that are relatively low amplitude,monophasic signals, may be more readily sensed when the active surfacearea of the electrode is increased. Moreover, an evoked responsefollowing delivery of a stimulation pulse may be more readily detectedwhen post-pace polarization artifact is diminished.

Recently, as reported in the Journal of the American Chemical Society(JACS), research personnel at Washington University in St. Louis andtheir collaborators report that they have made boron “nanowhiskers” bychemical vapor deposition. The particles have diameters in the range of20 to 200 nanometers and the whiskers (also called nanowires) aresemiconducting and show properties of elemental boron.

The group at Washington University in St. Louis turned to boron, onespot to the left of carbon in the periodic table, to see if it would bea good candidate. They postulated that if nanotubes could be made ofboron and produced in large quantities, they should have the advantageof having consistent properties despite individual variation in diameterand wall structure. The discovery that the “nanowhiskers” aresemiconducting make them promising candidates for nanoscale electronicwires. Boron nitride nanotubes, which are similar in structure to carbonnanotubes, are electrically insulating. Boron nanotubes on the otherhand may be grown into long thin wire-like structures. At first theyappeared hollow, but after closer examination, they were determined tobe dense whisker-like structures, not hollow nanotube structures. Thenotion of boron nanotubes creates more excitement in nanotechnology thannanowhiskers because of their unique structure, which could be likenedto a distinct form of an element. Carbon, for instance, is present asgraphite and diamond, and, recently discovered, in “buckyball” andnanotube configurations. Also, boron nanotubes are predicted by theoryto have very high conductivity especially when bulk boron is “doped”with other atoms to increase conductivity. Carbon nanotubes also havebeen doped, as have various other kinds of nanowires, and assembled incombinations of conducting and semiconducting ones to make for severaldifferent microscale electronic components such as rectifiers,field-effect transistors and diodes.

SUMMARY OF THE INVENTION

The present invention is directed at providing a class of improvedmedical electrical lead assemblies featuring carbon nanotube material.Carbon nanotubes, discovered in about 1991, are formed from a cage-likehollow lattice structure of carbon molecules arranged into tubes havinga diameter on the order of nanometers. Considerable interest in the useof carbon nanotubes in various applications such as batteries,capacitors, flat panel displays and microelectronics, has grown due tothe unique properties of this newly discovered material including itshigh strength, stable state, low weight, and so-called ballistic (ornear-superconducting) electrical properties. In addition, boronnanotubes and carbon nanotube “nanowires” are now becoming available.The inventors have discovered that these developments enable inventionof discrete technologies providing significant value to patientssuffering from diverse afflictions while advancing the medical devicefield in several important ways.

Nanotubes made exclusively from carbon are chemically inert and aretherefore potentially biocompatible. Carbon nanotubes may be formed tohave metallic conductor or semi-conductor properties and are capable ofsustaining a high current density, which may be on the order of hundredsof times greater than common metals. Carbon nanotubes are thin, longtubular macromolecules with diameters on the order of a 1-200 nanometers(molecules are on the order of a few nanometers) and with lengths on theorder of micrometers to millimeters. Bundles of such nanotubes createnanostructures which are characterized by a large surface area andhighly anisotropic properties. In short, these characteristics of carbonnanotubes may make them particularly well-suited for diverse uses inconjunction with medical electrical lead assemblies and medicalelectrodes for improving electrode performance.

The present invention utilizes carbon nanotubes to render greatlyimproved medical electrical leads and/or medical electrodes. The presentinvention provides such leads and/or electrodes in one or more of thefollowing ways. Nanotube structures coupled to, layered upon or coatedupon a electrically conductive or non-conductive electrode or lead bodystructure. In addition, a variety of polymers and polymer-basedmaterials when combined, encapsulated or impregnated with nanotubes canbe used to render the resulting structures electrically conductive. Inthe context of the present invention, such structures may be configuredas elongated medical lead body structures, electrode structures and thelike. In addition, carbon nanotubes and their compounds with othermaterials may be employed in lieu of a metallic coil conductor (or othertype) of primary electrical conductor for all or a portion of the bodyof an extremely thin, resilient and flexible medical electrical lead.The resulting structure may be porous and itself impregnated withdiverse materials such as steroid material, electrically conductivefluid or paste materials, and the like.

One embodiment of the present invention features a medical electricallead carrying one or more tip-, ring-, defibrillation coil-,neurological-, brain-, skeletal muscle-, or organ-electrodes for sensingand/or delivering electrical stimulation pulses to a portion of cardiactissue, neurological tissue, brain tissue, skeletal tissue, organ tissueand the like.

In embodiments involving cardiac tissue, the active surface area of theelectrodes, which is contact with blood or bodily tissue, is increasedby depositing carbon nanotubes on the electrode surface. Furthermore,carbon nanotubes at the electrode/tissue interface emit electrons fromthe tip portions of the nanotubes at relatively low voltages and sustaincurrent densities hundreds of times greater than common metals. Suchfield emission properties can be obtained by mixing nanotubes into acomposite paste with polymers such as polyurethane or silicone, applyingthe paste to an electrode surface, and then applying a voltage to alignthe nanotubes on end. Such alignment can form extremely consistent,tightly packed arrays of nanotubes or may be less consistent. In eithercase, a vast surface area is created which is very advantageous as isknown to those of skill in the art. Such arrays of nanotubes may beimpregnated with diverse materials such as biological, genetic orpharmacological substances so that over time said arrays elute thematerials into adjacent tissue or body fluid. Some representativediverse materials include steroid material, electrically conductivefluid materials such as isotonic saline solution or other biologicallycompatible fluids.

In another embodiment, a carbon nanotube coating may be applied to ametallic electrode substrate, such as platinum, platinum-iridium,titanium, alloys of the foregoing and other metals by chemical vapordeposition or other methods known in the art for growing and depositingcarbon nanotubes on a substrate. The surface area of the carbonnanotubes, which may include the outer surface and the inner surface ofthe tubes, effectively increases the active electrode surface area ofthe metallic electrode substrate.

The carbon nanotube coating provides a highly biocompatible electrodesurface. Moreover, the carbon nanotube coating provides a lowelectrode-tissue interface impedance allowing for improved sensing oflow frequency, intrinsic cardiac signals as well as evoked responsesfrom cardiac tissue. The high-energy density properties of carbonnanotubes further provides lower stimulation thresholds for capturing aheart during pacing and/or when delivering defibrillation therapy to aheart.

While chemical vapor deposition (CVD) represents one manner of massproducing apparatus according to the present invention, CVD generallyhas a higher density of structural defects and a subsequently a largervariation in resistivity. Metallic catalysts such as nickel, iron,cobalt, molybdenum and ruthenium are usually necessary for formation ofconsistent, high yield films using CVD. Achieving good contactresistances to the substrate material is still a matter of adapting thecatalyst and substrate to one another, among other variables. If theformation of thin oxide layers, on the atomic scale, occur between thenanotubes and metal substrate, high ohmic-contact resistance is oftenthe result. As research continues with respect to high yield, massproduction of carbon nanotube coatings, there are now presentlyavailable highly ordered single-wall and multi-wall nanotube structureson substrates in a very ordered manner.

In this patent disclosure the term “nanotube(s)” is intended to refer tonanostructures in general; that is, substantially zero dimensionalstructures such as quantum dots, one dimensional so-called nanowires (or“nanowhiskers”), two dimensional, substantially planar structures, andthree-dimensional structures such as closed- and open-ended nanotubes,and the like. The inventors suggest that when incorporated into suitablyadapted structures the fully variety of nanostructures may be used toimprove the electrical performance of myriad medical electrical leads.In some applications, the nanostructures may also be used to retainand/or release over time the above-noted diverse materials, such aselectrically conductive fluids, biological, genetic and/orpharmacological substances. Thus, the terms used in the present patentdisclosure may differ from the evolving convention(s) for referring to abroad variety of different nano-scale structures. For example,typically, a nanotube is any tube having nanoscale dimensions, but isoften intended to generally refer to carbon nanotubes. In thisdisclosure the reverse is true. Thus, in this disclosure “nanotube” or“nanostructure” is intended to include carbon nanotubes and othernanostructures, and shall also be deemed to cover an often mentionednon-carbon variety of nanotube made of boron and the like. In general,then, nanotubes are sheets of graphite rolled up to make a tube. Thedimensions are variable (down to 0.4 nm in diameter) and a singlenanotube can be formed or disposed within another nanotube, leading to adistinction between multi-walled and single-walled nanotubes (“MWNT” and“SWNT,” respectively).

Apart from remarkable tensile strength, nanotubes exhibit varyingelectrical properties (depending on the way the graphite structurespirals around the tube, and other factors), and can be insulating,semiconducting or conducting (metallic).

Nanotubes can be either electrically conductive or semiconductive,depending on their helicity, leading to nanoscale wires and electricalcomponents. These one-dimensional fibers exhibit electrical conductivityas high as copper, thermal conductivity as high as diamond, strength 100times greater than steel at one sixth the weight, and high strain tofailure.

Carbon nanotubes exhibit extraordinary mechanical properties: theYoung's modulus is over 1 Tera Pascal and as stiff as diamond with anestimated tensile strength of about 200 Giga Pascal. These propertiesare ideal for reinforced composites and nanoelectromechanical systems,among others.

Carbon nanotube transistors exploit the fact that nm-scale nanotubes areready-made molecular wires and can be rendered into a conducting,semiconducting, or insulating state, which make them valuable for futurenanocomputer design. Carbon nanotubes have generated considerableinterest for their prospective electrical, thermal, and evenselective-chemistry applications.

While the present invention will be described primarily with referenceto single- and multi-walled carbon nanotubes (SWNT/MWNT), it is not tobe construed as being limited solely to such materials. For example, thepresent invention may be practiced using so-called “nanowires” or“nanowhiskers” (NW). Such NW may be produced of carbon or other relatedelements such as boron and the NW (and SWNT/MWNT) may be doped ormodified so they readily conduct electricity, are semi-conductive, oreven insulative.

The foregoing summary is intended to briefly introduce the reader to thebasic concepts of the present invention and should not be construed aslimiting the invention hereof. Likewise, the following drawings (andthose incorporated herein) are illustrative of only a few embodiments ofthe present invention, are not drawn to scale and should not be viewedas limiting the scope of the present invention. In fact, those of skillin the art will quickly recognize variations of the described anddepicted embodiments of the present invention, and each such variationis intended to be covered by this patent disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a plan view of a cardiac pacing lead that may be used inconjunction with the present invention. It should be noted that thepacing lead may have one or more anode rings.

FIG. 1B is a plan view of the distal end of a cardiac pacing anddefibrillation lead that may be used in conjunction with the presentinvention.

FIG. 2 is a flow diagram summarizing a method for manufacturing a carbonnanotube coated medical electrode.

FIG. 3 is an illustration of a magnified, side view of a carbon nanotubecoated electrode wherein the nanotubes are aligned.

FIG. 4 is an illustration of a magnified, side view of a carbon nanotubecoated electrode wherein the nanotubes are randomly ordered.

FIG. 5 is an illustration of a magnified, side view of a carbon nanotubecoated electrode wherein the nanotubes are coiled and randomly arranged.

FIG. 6 is a flow chart summarizing an alternative method formanufacturing a carbon nanotube coated medical electrode.

FIG. 7 is a flow chart summarizing steps performed in a method formanufacturing a nanostructure coated medical device.

FIG. 8 is a graph comparing the frequency-dependent impedancecharacteristics of a bare platinum-iridium (Pt—Ir) electrode and acarbon nanostructure coated electrode.

FIG. 9 is a graph of the post-pulse electrode polarization response of acarbon nanostructure coated electrode compared to bare Pt—Ir electrodeand a Pt—Ir electrode coated only with a conductive polymer.

DETAILED DESCRIPTION OF THE INVENTION

As described above, the present invention is directed at providing amedical lead having improved electrode performance by providing carbonnanotube coated electrodes. FIGS. 1A and 1B depict exemplary medicalleads of the type that may be used with the present invention. FIG. 1Ais a plan view of a medical lead 10 that may typically be used forcardiac pacing and/or sensing. Lead 10 is provided with an elongatedlead body 12, a helical tip electrode 14 located at the distal end ofthe lead and a ring electrode 16 spaced proximally from tip electrode14. A connector assembly 18 at the proximal end of lead 10 is used toconnect the lead to a medical device, such as a pacemaker. Conductorsextending the length of lead body 12 electrically couple the tipelectrode 14 and ring electrode 16 to respective connectors carried bythe connector assembly 18.

FIG. 1B is a plan view of the distal end of a medical lead 20 of thetype that may be used for pacing, sensing, cardioversion and/ordefibrillation. Lead 20 is provided with a tip electrode 22 and a ringelectrode 24, which are generally used for pacing and/or sensing, andtwo defibrillation coil electrodes 26 and 28 for delivering high-energyshocking pulses for cardioversion or defibrillation.

The exemplary leads 10 and 20 of FIGS. 1A and 1B are shown to illustratethe various types of electrodes, including ring electrodes (16 and 24),coil electrodes (26 and 28), helical electrodes (14), or generallyhemispherical electrodes (22), with which the present invention may beused. Other electrodes of various geometries may exist that may alsobenefit from the use of carbon nanotube coating as provided by thepresent invention. The application of the present invention is thereforenot limited to the types of electrodes depicted in FIGS. 1A and 1B. Thepresent invention may also be used in conjunction with electrodes forneurological stimulation or sensing, smooth or skeletal muscle sensingor stimulation or any other types of medical electrodes that may benefitfrom increased active surface area and/or increased current densitycapacity.

An electrode used with the present invention is preferably fabricatedfrom a conductive biocompatible material appropriate for depositingcarbon nanotubes thereto. CVD methods begin with supported catalystparticles that are exposed to a carbon feedstock gas (e.g., acetylene ormethane). Carbon atoms from the dissociation of these molecules at thecatalyst surface dissolve in the catalyst particles to reappear on thesurface, where they organize to form nanotubes. Depending on the growthconditions (e.g. gas mixture, gas flows, reaction temperature, reactiontime, and catalyst), the catalyst particle either remains on the surface(base growth) or is lifted from the surface by the nanotube (tipgrowth).

As mentioned earlier, adapting the catalyst to the substrate iscritically important and note that catalysts can also be deposited tothe substrate surface before introducing the carbon nanotubes. Noblemetal substrates such as gold are known to suppress growth. The problemis most likely due to alloy formation with the catalyst material.Refractory metals and their nitrides can act as a diffusion barrier tothe chosen catalyst. Also, applying an AC or DC electric field helps innanotube growth.

The electrode material may be, for example, platinum, platinum-iridium,iridium, titanium or alloys, tantalum, and other non-noble metals. Theelectrode surface may also be treated or coated to enhance the surfacefor nanotube deposition, as will be further described below.

Carbon nanotubes may be grown and deposited onto a surface by at leastthree methods: 1) chemical vapor deposition, 2) carbon arc deposition,and 3) laser evaporation deposition. Chemical vapor deposition methodsgenerally use a metal catalyst substrate at a high temperature to whicha hydrocarbon gas is exposed. Carbon nanotubes are deposited on thecatalyst surface and may be grown in various structures such as straighttubes that may be well-aligned or coiled tubes. A method for growingdensely packed, uniform nanotube arrays perpendicular to a substrate isgenerally disclosed in U.S. Pat. No. 6,361,861 issued to Gao et al.,incorporated herein by reference in its entirety.

Carbon arc deposition methods include evaporating material from agraphite electrode in an electric arc discharge between two graphiteelectrodes. Carbon nanotubes deposit on the other graphite electrode andare generally straight but may be impure with a high percentage ofnanoparticles. Laser evaporation techniques involve forming carbonnanotubes in a plume of carbon vapor evaporated from a graphite targetby a laser at high temperature.

Methods for growing and depositing carbon nanotubes on a substrate mayproduce varying purity, density, alignment, structure, and size of thenanotubes. Carbon nanotubes are formed as one or more concentric shellsof graphite and therefore may be single-walled, double-walled ormulti-walled tubes. Nanotubes may be straight or may have irregularcurving or coiling shapes. Nanotubes reportedly range in diameter from 1nanometer to several hundred nanometers. Nanotubes may be grown to be onthe order of 1 micron to several hundred microns in length. Futuremethods for carbon nanotube growth and deposition may be developed thatimprove the purity, increase uniformity or achieve desired geometries orproperties of the nanotubes, such as desired electrical properties.

In the present state of the art, carbon nanotube coated electrodes arecontemplated to be produced by chemical vapor deposition methods, thoughany of the above described methods or modifications thereof or newlydeveloped methods may be used. FIG. 2 is a flow chart depicting onemethod for producing a carbon nanotube coated electrode. The method maybegin by preparing an electrode surface for deposition of the carbonnanotubes at step 102. The electrode is preferably fabricated fromplatinum or platinum-iridium. The electrode may take the form of anyknown types of electrodes, such as those shown in FIGS. 1A and 1B. Theplatinum iridium surface of the electrode may be a sufficient catalystfor carbon deposition. Alternatively, the electrode surface may beprepared by creating a more porous surface and/or coating the surfacewith an alternative biocompatible catalyst to promote strong bonding ofthe carbon nanotubes to the electrode surface or to enhance thedeposition process. For example, a platinum electrode may be coated witha porous coating of catalytic nanoparticles. The porous coating mayprovide a better catalyst for carbon nanotube deposition in that thegrowth direction, size, and density of the nanotubes may be controlledby the pores (see Li et al., Science, 1996; 274(5239):1701-3.

The electrode may then be mounted in a vacuum chamber at step 104through which an inert gas flows, such as a helium-argon gas, to raisethe pressure in the chamber at step 106. The temperature of thesubstrate is raised at step 108. The temperature may typically be raisedto a level on the order of 500 to 1000 degrees C. Resistive heatingelements may be used to heat the substrate, although other equivalentmeans may be employed.

A carbon source in the form of a hydrocarbon gas, which may be, forexample, acetylene gas, methylene gas, or ethylene gas, is then allowedto flow through the chamber at step 110. At step 112, nanotubedeposition and growth are allowed to occur. The time required foradequately coating the electrode surface with a carbon nanotube coatingmay range from several minutes to several hours. The size of thenanotubes and their uniformity and density may be controlled by the flowrate of the hydrocarbon gas, the temperature of the substrate, thedensity of the catalyst on the substrate or other conditions.

Verification of the carbon nanotube coating may be performed by scanningelectron microscopy or other methods at step 114. Verification may beperformed to ensure a desired density or size of the nanotubes has beenachieved or to ensure that the nanotubes are well attached to theelectrode surface. The carbon nanotube coated electrode may then beassembled onto a lead at step 116 and electrically coupled to aconductor extending through the lead body.

Nanotubes may be deposited in an orderly, aligned fashion using variousdeposition methods. FIG. 3 is an illustration of a side view of anordered nanotube “forest” 30 as it may be deposited on the surface of anelectrode 32. The nanotube “forest” 30 may be grown such that thenanotubes are well aligned with one another and each generally have oneend attached to the electrode surface. The nanotubes may be on the orderof 0.1 to 300 microns in length and one to 200 nanometers in diameterdepending on the deposition method used. A preferred range of diametersis in the range of approximately about one nm to about 20 nm but thepresent invention is not to be strictly limited to this range. Incertain embodiments of the present invention a highly ordered array ofSWNT members disposed approximately perpendicular to a supporting memberhaving a diameter dimension on the order of approximately about one toabout five nm diameters. But that does not mean an excellent electrodecouldn't be had with random MWNT's about 200 nm diameter in a urethanepaste and the like.

FIG. 4 illustrates an alternative arrangement of deposited nanotubes ona medical electrode surface. Nanotubes 36 may be deposited in adisorderly fashion wherein nanotubes 36 are straight but not alignedwith respect to each other. The tubes will still have one end generallyattached to the electrode surface 38.

FIG. 5 illustrates yet another arrangement of deposited nanotubes 40 ona medical electrode surface 42. In this embodiment, coiled nanotubes 40,having one end attached to the electrode surface 42, are arrangedrandomly on electrode surface 42. Deposition methods resulting in coilednanotubes have been described previously in the prior art.

The paste method described earlier is a preferred manner of couplingnanostructures to chronically implanted medical devices. In analternative embodiment, carbon nanotubes may be grown and purified in afirst process and then deposited onto an electrode surface as a coatingin a second process. A method for depositing a purified carbon nanotubematerial onto a conductive substrate is generally disclosed in U.S. Pat.No. 6,280,697 issued to Zhou et al., incorporated herein by reference inits entirety.

FIG. 6 is a flow chart summarizing this alternative method formanufacturing carbon nanotube coated electrodes. Carbon nanotubes aregrown at step 122 and purified at step 124. For example, carbonnanotubes may be formed by arc or laser deposition methods, or any knownmethod, and purified by an appropriate method such as filtering througha microporous membrane. Alternatively, carbon nanotube materials thatmay be suitable for coating medical electrodes may be obtained directlyfrom commercial sources such as NanoLab, Brighton, Mass.; CarboLex,Lexington, Ky.; Materials and Electrochemical Research Corporation,Tucson, Ariz., among a growing number of other suppliers.

At step 126, the nanotubes are suspended in a solvent, such as alcohol.An electrode to be coated may then be placed in a vessel with thesuspension of carbon nanotubes at step 128. The solvent is then drivenoff at step 130 leaving a coating of nanotubes on the surface of theelectrode. The nanotube coating may be verified at step 132 as describedabove. The electrode may then be assembled onto a medical lead at step134.

The increase in active surface area created by a carbon nanotube coatingis expected to be a minimum of 1,000× to potentially on the order ofabout 10,000×. This increase is theorized to result in a reduction ininterfacial impedance at low frequencies from approximately 1000×,associated with prior known electrode coating methods such as sputteredporous titanium nitride, and iridium oxide. That is, the increase inactive surface area created by a carbon nanotube coating is expected tobe on the order off 1,000 to about 10,000×. The low frequencies referredto hereinabove, are on the order of less than about 0.1 Hz (or lower).Such a decrease in interfacial impedance improves electrode sensingperformance which is very important for certain medical applications,such as cardiac rhythm management. This reduction in interfacialimpedance and the high current density properties of carbon nanotubesalso reduces pacing and/or defibrillation thresholds.

Methods for increasing the defects in the walls of the depositednanotubes or for opening the ends of the tubes may be used to furtherincrease the active surface area of the electrode. For examplemechanical ball-milling or exposure to ultrasonic energy as generallydisclosed in U.S. Pat. No. 6,280,697 may be applied to increase theavailable, accessible surface area. Theoretically, by creating moreopenings in the nanotubes, electrolytes may enter the tubes, which wouldexpectedly further reduce the interfacial impedance, improving theelectrode performance.

FIG. 7 is a flow chart summarizing steps performed in a method forfabricating a nanostructure coated medical device. The performance ofthe implantable medical device may be improved by a reduction of theinterfacial impedance provided by a nanotube or other nanostructurecoating. The medical device may be a low-voltage electrode, high-voltageelectrode, a portion of an implantable medical device housing, abiosensor, or other implantable medical device.

Method 200 includes applying an adhesion layer to the medical devicesubstrate on which the nanostructures may be deposited. At step 205, anadhesion layer is applied to the medical device by coating the desiredsurface area of the medical device with a conductive polymer coating.The polymer coating can be formed from a polymer base with a conductiveadditive. The polymer base is a medical grade polymer havingbiocompatibility properties appropriate for the intended use of themedical device. The polymer base may be, for example, polyurethane,epoxy, silicone or a hydrogel. The polymer base is made conductive bydoping the polymer with a conductive material such as a carbon-basedmaterial or another biocompatible conductive material. In someembodiments, the polymer base may be made conductive by doping thepolymer with carbon black or with conductive carbon nanotubes or othernanostructures.

Alternatively the conductive polymer coating may be formed of aninherently conductive polymer, such as polypryrrole. An inherentlyconductive polymer may be also be doped with a conductive material suchas carbon black or conductive carbon nanotubes or other nanostructures.

The conductive polymer coating may be less than 1 micron to severalmicrons in thickness, although greater thicknesses may be suitable forcreating an adhesion layer to which a coating of nanostructures can beapplied. Practice of the present invention is not limited to an adhesionlayer of a particular thickness.

In one embodiment, the conductive polymer coating is annealed to themedical device substrate at step 210. The conductive polymer coating isannealed, or treated to reflow, to cause formation of a conformableinterface between the conductive polymer coating and the substratesurface. Reflow of the conductive polymer coating can be accomplished byheating the polymer coating to at least about the melt flow temperatureof the polymer for a time sufficient to reflow the polymer. Reflow canalternatively be achieved by using thermal treatment, infraredtreatment, microwave treatment, RF treatment, mechanical treatment suchas compression or shearing, or solvent treatment. Annealing step 210 maybe performed according to the methods generally disclosed in U.S. Pat.App. No. P-10753, incorporated herein by reference in its entirety.Annealing step 210 can be performed in air but may be preferentiallyperformed in an inert gas such as nitrogen.

Annealing the conductive polymer coating can improve adhesion of theadhesion layer to the underlying medical device substrate. Inexperiments performed by the inventors, annealing a polyurethane coatingdoped with carbon black improved the adhesion of the coating to aPlatinum-Iridium electrode substrate as found by performing tape tests.Annealing was performed at 220 degrees Celsius in air for 5 minutes.

If annealing is performed, at step 210, a second conductive polymercoating is applied at step 215. Typically the second coating is arelatively thinner coating than the first coating. The second coating isapplied to provide an adhesive surface on to which the nanostructurecoating can be applied. The nanostructure coating is applied at step 220by dipping the device in a nanostructure powder prior to allowing thesecond conductive polymer coating to cure. Thus, the adhesion layer isformed of two conductive polymer coatings with the first coatingannealed to the medical device substrate to promote adhesion to thesubstrate and the second coating providing an adhesive surface on whichto deposit the nanostructures.

If the annealing step 210 is not performed, the nanostructure coatingmay be applied at step 220 by dipping the device in a nanostructurepowder prior to allowing the first conductive polymer coating to cure. Asecond conductive polymer coating is not necessary for providing anadhesive surface for attaching the nanostructures. Thus, in someembodiments, the adhesion layer is formed of a single conductive polymercoating.

In other embodiments, the adhesion layer is formed of a first conductivepolymer coating, which may be annealed to the substrate surface forenhanced adhesion, and a second conductive polymer coating. By applyingthe second conductive polymer coating, greater flexibility is gainedduring manufacturing processes since the nanostructures can be appliedafter the first conductive polymer coating has cured.

Prior to dipping the medical device in the nanostructures at step 220,the nanostructures may be purified at step 218 to achieve desiredelectrical properties of the nanostructure coating. For example, pureconductive nanotubes may be separated from semi-conductive and resistivenanotubes.

After applying the nanostructure coating, the conductive polymer coatingis allowed to cure at step 225. The conductive polymer coating that isallowed to cure at step 225 is either a first conductive polymer coatingthat has not been annealed or a second conductive polymer coating thatis applied over a cured or annealed first conductive polymer coating.The curing time and conditions (e.g., temperature, gas exposure,humidity) are suitably selected for the type and thickness of thepolymer applied.

FIG. 8 is a graph of frequency-dependent impedance characteristics of aplatinum-iridium (Pt—Ir) electrode. A comparison of frequency-dependentimpedance measurements was made for the bare platinum-iridium electrodesubstrate, the Pt—Ir substrate coated with a conductive polymer, and thePt—Ir substrate coated with a conductive polymer and carbon nanotubes.In this example, the conductive polymer was 75D polyurethane doped with20% carbon black.

The conductive polymer coating had an effect of increasing thelow-frequency impedance response of the Pt—Ir electrode substrate.However, the addition of the carbon nanotube coating on top of theconductive polymer coating resulted in about a 100-fold decrease inimpedance compared to the Pt—Ir substrate alone.

FIG. 9 is a graph of the post-pulse electrode polarization response of acarbon nanotube coated electrode compared to bare Pt—Ir electrode and aPt—Ir electrode coated only with a conductive polymer. The post-pulsepolarization voltage was measured 20 ms after application of astimulation pulse. The conductive polymer coating (75D polyurethanedoped with 20% carbon black) caused the post-pulse polarization voltageto increase compared to the bare Pt—Ir electrode post-pulse polarizationvoltage. The addition of a coating of carbon nanotubes applied over theconductive polymer coating resulted in about a 20-fold decrease inpost-pulse polarization voltage. Thus, an improvement in the electricalproperties of the Pt—Ir electrode was achieved by application of acarbon nanostructure coating using a conductive polymer adhesion layer.The benefit of the carbon nanostructure coating is expected to berelated to the increase in active surface area of the electrode.

An improved medical lead having carbon nanostructure coated electrodesand method for manufacture provided by the present invention has beendescribed according to specific embodiments. It is recognized that oneknowledgeable in the art may conceive variations of these embodimentsthat generally gain the benefits provided by a carbon nanostructurecoated electrode. The above described embodiments should therefore notbe considered limiting in regard to the following claims.

1. A method for manufacturing a medical device, comprising: applying an adhesion layer to a medical device substrate; and depositing a plurality of nanostructures onto the adhesion layer.
 2. The method of claim 1 wherein applying the adhesion layer comprises applying a first coating of a conductive polymer to the at least a portion of the medical device.
 3. The method of claim 2 wherein applying the adhesion layer further comprises annealing the first coating of the conductive polymer to the medical device substrate.
 4. The method of claim 3 wherein applying the adhesion layer further comprises applying a second coating of the conductive polymer over the annealed first coating of the conductive polymer.
 5. The method of claim 4 wherein depositing the plurality of nanostructures onto the adhesion layer comprises dipping the adhesion layer coated medical device substrate into a nanostructure powder prior to allowing the second conductive polymer coating to cure.
 6. The method of claim 4 wherein depositing the plurality of nanostructures onto the adhesion layer comprises dipping the adhesion layer coated medical device substrate into a composition that contains dispersed nanostructure materials prior to allowing the second conductive polymer coating to cure.
 7. The method of claim 2 wherein the conductive polymer comprises a biomedical grade polymer base doped with a conductive additive.
 8. The method of claim 7 wherein the conductive additive comprises a carbon-based additive.
 9. The method of claim 8 wherein the conductive additive comprises carbon black.
 10. The method of claim 7 wherein the conductive additive comprises nanostructures.
 11. The method of claim 2 wherein the conductive polymer comprises an inherently conductive polymer.
 12. The method of claim 2 wherein the conductive polymer comprises an inherently conductive polymer doped with a conductive additive.
 13. The method of claim 12 wherein the conductive additive comprises nanostructures.
 14. A medical device, comprising: an adhesion layer formed of a conductive polymer coating applied to at least a portion of a surface of the medical device; and a plurality of nanostructures deposited onto the adhesion layer.
 15. The medical device of claim 14 wherein the conductive polymer coating is annealed to the at least a portion of the surface of the medical device. 